Chemical Origins of Life

Sudha Rajamani INSA Meeting 2017

Indian Institute of Science Education and Research Pune, India

Early history of life on Earth

Prebiotic chemistry leading to formation of building blocks

Nonenzymatic polymerization leading to emergence of polymers Formation of primitive membranes

Nonenzymatic replication

Emergence of protocells capable of Darwinian evolution

Steps leading to the emergence of a primitive cellular entity (protocell)

Oparin-Haldane Theory

Basic hypothesis: Early Earth’s atmosphere was reducing (had an excess of negative charge, could cause reducing reactions by adding electrons to compounds). Under these conditions, organic molecules could have formed from simple inorganic molecules.

http://hyperphysics.phy-astr.gsu.edu/nave-html/faithpathh/lifelab.html

The ideas of these two men were simple, elegant, and almost identical!

Methane

http://www.cbs.dtu.dk/staff/dave/roanoke/primsoup.jpg

Haldane’s “Primordial Soup”: The primordial sea served as a vast chemical laboratory powered by solar energy where the atmosphere was oxygen free. Host of organic compounds formed under these conditions became a 'hot dilute soup' containing large populations of organic monomers and polymers.

Glycine

Methane

Water

Ammonia

Alanine

Formic acid

Lactic acid

Glycolic acid

Urea

Glutamic acid

Acetic acid

The Miller-Urey Experiment (1953)

Serine

Environments that would have supported life-producing chemical reactions

http://www.photolib.noaa.gov/htmls/nur04506.htm

David Deamer, Bumpass Hell, Mount Lassen, CA, USA

Damer and Deamer, http://www.mdpi.com/2075-1729/5/1/872

Damer and Deamer, http://www.mdpi.com/2075-1729/5/1/872

Damer and Deamer, http://www.mdpi.com/2075-1729/5/1/872

“A recipe for life itself? Precursors to amino acids, nucleosides and lipids can all be obtained from the same simple starting materials.” - Paul J. Bracher, in News and Views of Nature Chemistry , 7, 273–274 (2015)

Formation of RNA by nonenzymatic oligomerization

Polymerization in biology is achieved by use of high energy monomers and enzymes

Early oligomerization had to be nonenzymatic & by chemical means

Chemical polymerization is predominantly condensation reaction, driven by fluctuating dehydration-rehydration cycles, a common theme on prebiotic Earth

Not favorable in bulk solution due to excess of water

Polymerization is an uphill reaction

Most studies use activated nucleotides

- H2O

Monomers Oligomers

Mixture of Biomolecules

Oligomers Polymers with complex functions

Originate?

Evolve?

Condensation reactions result in polymerization

Use of activated nucleotides for oligomerization

Polymerization favorable if monomers are high energy molecules

Modern biology uses activated monomers such as triphosphates, animoacyl-tRNAs etc

For chemical polymerization, monomers are activated using better leaving groups

Several studies have used imidazole activated nucleotides

Activated nucleotides polymerize faster giving better yields

Joshi and Ferris, JACS (2009)

Polymerization mechanisms

Surface- mediated catalysis

Eutectic phases in

Ice - water

Amphiphiles as organizing

surfaces

Nonenzymatic polymerization

Surface-mediated catalysis

Polymerization in aqueous solutions is a chance event due to diffusional mobility

Adsorption onto surfaces bring monomers closer and also increases their local concentration

Studies on surface-mediated catalysis use clay as catalyzing agents

Clay thought to be abundant on prebiotic Earth

Clay has large surface area to volume ratio

Internal structure is lattice-like with several ions present in interlayers, spaces where polymerization is favoured

Joshi et. al., JACS (2009)

Eutectic phases in Ice-Water

Dilute solutions of salt show eutectic freezing

Eutectic phases result in selective exclusion of solute molecules from ice crystals thus increasing the effective concentration

Formation of nucleobases from HCN & cyanoacetylene at low temp.

Polymerization of imidazole activated nucleotides under eutectic conditions is observed

Freezing is required for efficient polymerization &

not just low temp.

Unfavorable back reactions (hydrolysis) prevented

Kanavarioti, Astrobiology (2001); Monnard, JACS (2003); Menor, Chem. Soc. Rev. (2012)

Amphiphiles on prebiotic Earth

Biomolecules such as phospholipids, fatty acids are amphiphiles and are components of cell membranes

Fatty acids as candidate for primitive membranes Fatty acids have shown to be synthesized by Fisher-Tropsch-Type reactions Mixed fatty acids form vesicles in high ionic strength solutions and at very

low & high pH regimes

Stabilized by addition of various polycyclic aromatic compounds

Some compositions selectively permeable for biomolecules seen in extant biology (ribose over other sugars)

Apel et. al. Biochemia et Biophysia Acta (2002); Sacerdote et. al., PNAS (2004); Namani, OLEB (2008)

Primitive FA membrane structures visualized by light microscopy

Monnard and Deamer, The Anatomical Record, 2002

Amphiphilic compounds extracted from the

Murchison meteorite

Vesicles formed from pure monocarboxylic

acids

Monocarboxylic acids with admixtures of PAH derivatives form vesicles when

exposed to dilute aqueous salt solutions at pH 7.0

Decanoic acid:decanol (37mM: 3mM, C10, pH 7.4)

Amphiphiles as compartments

Fatty acid vesicles show growth and division without external catalyst

Ribozymes have been shown to be functional inside vesicles

Competition is shown by vesicles containing active ribozymes. Vesicles containing active ribozymes can grow at expense of empty vesicles

Compartmentalization enhances functionality, facilitates prebiotic evolution and would have provided selective advantage in an “RNA World”

Chen, Biophys. (2004); Zhu and Szostak, JACS 2009; Chen, Roberts and Szostak, Science 2004; Chen, Salehi-Ashtiani and Szostak, JACS 2005

Amphiphiles as organizing matrix

Amphiphiles form higher order structures depending on concentration

Fluctuating environments common on early Earth which allow for formation of alternating hydrophobic & hydrophilic environments in multilamellar sandwiches

Monomers are ordered in these 2D spaces with diffusional

mobility. Structural analysis reveals arrangement of monomers in patterns that can favor bond formation

Non-activated RNA monomers and simpler sugar-phophate mononers are shown to polymerize in presence of amphiphiles at low pH & high temp Transfer of information by templated- replication also

possible

Rajamani et. al. OLEB (2008); Olasagasti et. al. Biochemie (2010); Deamer, Chem. Soc. Rev. (2012), Mungi and Rajamani, Life (2015)

Lipid-assisted oligomerization of non-activated nucleotides and sugar-phosphate monomers

Mungi and Rajamani, Life 2015

Chemical evolution: Primtive Genetic Polymers

Other heterocycles as information carrying units

OH +

Mungi, Singh, Chugh and Rajamani, Phys. Chem. Chem. Phys. 2016

Nucleotide formation with alternate bases

Hud et. al. Chemistry & Biology, 2013

Polymer fusion model

Mungi, Singh, Chugh and Rajamani, Phys. Chem. Chem. Phys. 2016

“The best we can ever do is to draw up a story that is consistent with all the evidence: with experiments in chemistry, with what we know about the early Earth, and with what biology reveals about the oldest forms of life. Finally, after a century of fractious effort, that story is coming into view.”

Saha R., Pohorille A. and Chen I.A., OLEB, 2014

https://www.toonpool.com/cartoons/intelligent%20life_17590

Da verrry best!!!!

COoL Lab Members and IISER Pune Biology

Jeet Chugh and Harshad IISER Pune Chemistry

Acknowledgments

Dr. Yayoi Hongo, Dr. Jim Cleaves, ELSI members

Chemical Origins of Life